Microtubules induce self-organization of polarized PAR domains in Caenorhabditis elegans zygotes

Nat Cell Biol. 2011 Oct 9;13(11):1361-7. doi: 10.1038/ncb2354.

Abstract

A hallmark of polarized cells is the segregation of the PAR polarity regulators into asymmetric domains at the cell cortex. Antagonistic interactions involving two conserved kinases, atypical protein kinase C (aPKC) and PAR-1, have been implicated in polarity maintenance, but the mechanisms that initiate the formation of asymmetric PAR domains are not understood. Here, we describe one pathway used by the sperm-donated centrosome to polarize the PAR proteins in Caenorhabditis elegans zygotes. Before polarization, cortical aPKC excludes PAR-1 kinase and its binding partner PAR-2 by phosphorylation. During symmetry breaking, microtubules nucleated by the centrosome locally protect PAR-2 from phosphorylation by aPKC, allowing PAR-2 and PAR-1 to access the cortex nearest the centrosome. Cortical PAR-1 phosphorylates PAR-3, causing the PAR-3-aPKC complex to leave the cortex. Our findings illustrate how microtubules, independently of actin dynamics, stimulate the self-organization of PAR proteins by providing local protection against a global barrier imposed by aPKC.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Genetically Modified
  • Caenorhabditis elegans / embryology
  • Caenorhabditis elegans / enzymology*
  • Caenorhabditis elegans / genetics
  • Caenorhabditis elegans Proteins / genetics
  • Caenorhabditis elegans Proteins / metabolism*
  • Cell Polarity*
  • Microtubules / enzymology*
  • Microtubules / genetics
  • Multienzyme Complexes
  • PDZ Domains
  • Phosphorylation
  • Protein Kinase C / genetics
  • Protein Kinase C / metabolism*
  • Protein Transport
  • Protein-Serine-Threonine Kinases / genetics
  • Protein-Serine-Threonine Kinases / metabolism*
  • RNA Interference
  • Recombinant Fusion Proteins / metabolism
  • Time Factors
  • Zygote / enzymology*

Substances

  • Caenorhabditis elegans Proteins
  • Multienzyme Complexes
  • Recombinant Fusion Proteins
  • par-2 protein, C elegans
  • PAR-1 protein, C elegans
  • PAR-3 protein, C elegans
  • Protein-Serine-Threonine Kinases
  • PKC-3 protein
  • Protein Kinase C